The proposed research project is a study of cyclic AMP-dependent protein kinase in gastric mucosa. It is currently hypothesized that the cAMP-dependent protein kinases are the receptors for cAMP and are responsible for the various effects of this nucleotide. It has been shown that protein kinase activation can be detected and measured even when intracellular cAMP levels are not significantly altered. Adenylyl cyclase activity has been shown to be stimulated in the gastric mucosa of frog, guinea pig, rabbit and man, but not in rat or dog. Conflicting results have also been obtained when tissue levels of cAMP were measured under various conditions of stimulation or inhibition of gastric secretion. Therefore, there exists a controversy regarding the mediating role of cAMP in gastric secretion. We plan to study the cAMP-dependent protein kinase activity in three species: rat, dog and guinea pig. Our aim is to investigate the effects of gastrointestinal hormones on the cAMP-dependent ppotein kinase activity. After administration of hormones, protein kinase activity will be determined by measuring the transfer of phosphate from ATP to a receptor protein, histone. This activity will be measured under appropriate conditions in both the presence and absence of added cAMP. Our aim is to further the knowledge of the molecular events which occur during gastric secretion, specifically the role of cyclic AMP as a possible mediator of this process.